Effects of Exercise and Obesity on Pancreatic Vasculature in Mice

Tausta. Kardiometaboliset sairaudet, kuten sydän- ja verisuonisairaudet, lihavuus ja tyypin 2 diabetes (T2D), ovat maailman yleisimpiä kuolinsyitä. Lihavuus ja siihen liittyvät aineenvaihduntasairaudet, kuten T2D, voivat heikentää hiussuoniston toimintaa eri elimissä. Koska hiussuonet mahdollistavat...

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Main Author: Hasu, Outi
Other Authors: Liikuntatieteellinen tiedekunta, Faculty of Sport and Health Sciences, Liikunta- ja terveystieteet, Sport and Health Sciences, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2024
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/97364
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author Hasu, Outi
author2 Liikuntatieteellinen tiedekunta Faculty of Sport and Health Sciences Liikunta- ja terveystieteet Sport and Health Sciences Jyväskylän yliopisto University of Jyväskylä
author_facet Hasu, Outi Liikuntatieteellinen tiedekunta Faculty of Sport and Health Sciences Liikunta- ja terveystieteet Sport and Health Sciences Jyväskylän yliopisto University of Jyväskylä Hasu, Outi Liikuntatieteellinen tiedekunta Faculty of Sport and Health Sciences Liikunta- ja terveystieteet Sport and Health Sciences Jyväskylän yliopisto University of Jyväskylä
author_sort Hasu, Outi
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description Tausta. Kardiometaboliset sairaudet, kuten sydän- ja verisuonisairaudet, lihavuus ja tyypin 2 diabetes (T2D), ovat maailman yleisimpiä kuolinsyitä. Lihavuus ja siihen liittyvät aineenvaihduntasairaudet, kuten T2D, voivat heikentää hiussuoniston toimintaa eri elimissä. Koska hiussuonet mahdollistavat solujen ja veren välisen ravintoaineiden sekä hengitysilman kaasujen ja kuona-aineiden vaihdon, muutokset niiden morfologiassa ja määrässä voivat merkitsevästi vaikuttaa kudosten toimintaan, aineenvaihduntaan ja yleiseen hyvinvointiin. Sekä ihmis- että hiiritutkimuksissa on huomattu T2D aiheuttavan morfologisia muutoksia haiman saarekkeiden verisuonissa, kun taas muualla haimassa verisuonet ovat enimmäkseen muuttumattomia. Vaikka fyysisen aktiivisuuden on osoitettu vähentävän aiemmin mainittujen sairauksien riskiä ja liikunnan merkitys on laajalti tunnustettu, sen positiivisia vaikutuksia solutasolla ei vielä täysin ymmärretä. Näin ollen tutkimuksen tavoitteena oli selvittää hiirimallinnuksen avulla ylipainon ja liikunnan aiheuttamia muutoksia haiman hiusverisuonten tiheydessä ja pinta-alassa. Menetelmät. Aikuiset C57BL/6J uroshiiret (n=40) jaettiin satunnaisesti neljään ryhmään: 1) hoikat liikkumattomat, 2) lihavat liikkumattomat, 3) hoikat liikkuvat, ja 4) lihavat liikkuvat. Lihavuus, hyperglykemia ja insuliiniresistenssi saatiin aikaan 18 viikon Western diet -ruokavaliolla. Liikuntaryhmille juokseminen mahdollistettiin kymmenennestä viikosta eteenpäin ja se jatkui aina tutkimuksen loppuun asti. Haimasta ja maksasta otetut ohutleikkeet värjättiin hematoksyliini-eosiinilla (H&E) ja immunofluoresenssin avulla. Haiman ohutleikkeiden kuva-analysointi tehtiin Fiji/ImageJ–kuva-analyysiohjelmalla. Parillista t-testiä käytettiin intervention ennen ja jälkeen -tulosten tulkintaan ja yksisuuntaista ANOVA-testiä käytettiin määrittämään erot eri hiiriryhmien välillä. Tulokset. Lihavien hiiriryhmien H&E-värjätyissä maksaleikkeissä rasvaa oli kertynyt selvästi enemmän hoikkiin hiiriin verrattuna. Lisäksi liikunnan huomattiin vähentäneen rasvan kertymistä maksaan. Haiman saarekkeiden verisuonissa ei havaittu merkitseviä muutoksia. Haiman eksokriinisessä kudoksessa verisuonten tiheys ja verisuonten suhde tumien lukumäärään olivat yleisesti ottaen suurempia lihavien hiirten ryhmissä verrattuna hoikkiin hiiriin. Lihavilla, liikuntaa harrastamattomilla hiirillä oli merkitsevästi suurempi verisuonten tiheys kuin hoikilla hiirillä. Lisäksi lihavilla liikuntaa harrastaneilla hiirillä oli merkitsevästi suurempi verisuonten tiheys kuin hoikilla liikkumattomilla hiirillä. Haiman saarekkeiden verisuonten tiheys, verisuonten suhteellinen osuus pinta-alasta ja Feret’n halkaisija olivat merkitsevästi suurempia kuin haiman eksokriinisen kudoksen. Johtopäätökset. Lihavilla hiirillä oli havaittavissa taipumusta kapillaarien laajenemiseen haiman saarekkeissa. Pidempi interventiojakso voisi paljastaa merkitsevämpiä muutoksia. Lihavien hiirten eksokriinisessä kudoksessa havaittu suurentunut verisuonten tiheys ja toisaalta pienempi Feret’n halkaisija voivat viitata angiogeneesiin, jossa yksi verisuoni jakautuu kahdeksi. Liikunnan vaikutus verisuonistoon oli vähäinen. Tulevaisuudessa tulisi ottaa huomioon ihmisverisuoniin kasautuvien amyloidikertymien vaikutus haiman verisuonistoon. Background. Cardiometabolic diseases, such as cardiovascular disease, obesity and type 2 diabetes, are the leading causes of death globally. Obesity and its associated metabolic diseases, like type 2 diabetes, can impair the microcirculation in different organs. Since vascular capillaries are the main site for substance exchange between cells and the vasculature, changes in their morphology and number can have serious effects on tissue function, metabolic health, and overall well-being. In the pancreas, type 2 diabetes has been shown to lead to morphological changes in both human and rodent intra-islet vasculature, while the exocrine vasculature remains mostly unaltered. Also, although physical activity has been shown to reduce the risk of these diseases, and despite the recognition of the importance of exercise, its positive effects at the cellular level are not yet fully understood. Therefore, this thesis aimed to investigate the changes that obesity and exercise induce on pancreatic capillary density and capillary area both together and separately using a mouse model. Methods. Adult C57BL/6J male mice (n=40) were randomized into four groups: 1) lean sedentary, 2) obese sedentary, 3) lean exercise, and 4) obese exercise. Obesity, hyperglycaemia and insulin resistance were induced using a Western diet for 18 weeks. Voluntary running for the exercise groups was started at ten weeks and lasted until the end of the study. Pancreas and liver sections were stained with haematoxylin-eosin (H&E) and with immunofluorescence. The image processing and analysis for pancreas sections were performed using Fiji/ImageJ software. A paired T-test was used to study changes between pre- and post-intervention and one-way ANOVA was used to determine differences between different mouse groups. Results. In H&E-stained liver sections, obese mice had visibly more lipid accumulation than the lean mice. Also, exercise was shown to reduce the lipid accumulation in the liver. In pancreatic islet capillaries, no significant differences were observed. In pancreatic exocrine tissue, the capillary density and capillaries-to-nuclei ratio were generally higher in obese groups compared to lean groups. In more detail, the obese sedentary group had significantly higher capillary density than both lean groups, and the obese exercise group had significantly higher capillary density than the lean sedentary group. All in all, compared to exocrine tissue, the pancreatic islets exhibited significantly higher capillary density, capillary area relative to tissue area, and capillary Feret's diameter. Conclusions. In islets, a trend toward possible capillary enlargement in obese groups suggests that subtle vascular changes might be occurring in response to high-fat feeding, and a longer intervention period could potentially reveal more pronounced effects. In exocrine tissue, significantly increased capillary density and slightly smaller Feret’s diameter in obese mice could indicate intussusceptive angiogenesis. The effect of exercise on vasculature was minor in both areas of pancreas. In future studies, the influence of amyloid deposits should be considered.
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Kardiometaboliset sairaudet, kuten syd\u00e4n- ja verisuonisairaudet, lihavuus ja tyypin 2 diabetes (T2D), ovat maailman yleisimpi\u00e4 kuolinsyit\u00e4. Lihavuus ja siihen liittyv\u00e4t aineenvaihduntasairaudet, kuten T2D, voivat heikent\u00e4\u00e4 hiussuoniston toimintaa eri elimiss\u00e4. Koska hiussuonet mahdollistavat solujen ja veren v\u00e4lisen ravintoaineiden sek\u00e4 hengitysilman kaasujen ja kuona-aineiden vaihdon, muutokset niiden morfologiassa ja m\u00e4\u00e4r\u00e4ss\u00e4 voivat merkitsev\u00e4sti vaikuttaa kudosten toimintaan, aineenvaihduntaan ja yleiseen hyvinvointiin. Sek\u00e4 ihmis- ett\u00e4 hiiritutkimuksissa on huomattu T2D aiheuttavan morfologisia muutoksia haiman saarekkeiden verisuonissa, kun taas muualla haimassa verisuonet ovat enimm\u00e4kseen muuttumattomia. Vaikka fyysisen aktiivisuuden on osoitettu v\u00e4hent\u00e4v\u00e4n aiemmin mainittujen sairauksien riski\u00e4 ja liikunnan merkitys on laajalti tunnustettu, sen positiivisia vaikutuksia solutasolla ei viel\u00e4 t\u00e4ysin ymm\u00e4rret\u00e4. N\u00e4in ollen tutkimuksen tavoitteena oli selvitt\u00e4\u00e4 hiirimallinnuksen avulla ylipainon ja liikunnan aiheuttamia muutoksia haiman hiusverisuonten tiheydess\u00e4 ja pinta-alassa. Menetelm\u00e4t. Aikuiset C57BL/6J uroshiiret (n=40) jaettiin satunnaisesti nelj\u00e4\u00e4n ryhm\u00e4\u00e4n: 1) hoikat liikkumattomat, 2) lihavat liikkumattomat, 3) hoikat liikkuvat, ja 4) lihavat liikkuvat. Lihavuus, hyperglykemia ja insuliiniresistenssi saatiin aikaan 18 viikon Western diet -ruokavaliolla. Liikuntaryhmille juokseminen mahdollistettiin kymmenennest\u00e4 viikosta eteenp\u00e4in ja se jatkui aina tutkimuksen loppuun asti. Haimasta ja maksasta otetut ohutleikkeet v\u00e4rj\u00e4ttiin hematoksyliini-eosiinilla (H&E) ja immunofluoresenssin avulla. Haiman ohutleikkeiden kuva-analysointi tehtiin Fiji/ImageJ\u2013kuva-analyysiohjelmalla. Parillista t-testi\u00e4 k\u00e4ytettiin intervention ennen ja j\u00e4lkeen -tulosten tulkintaan ja yksisuuntaista ANOVA-testi\u00e4 k\u00e4ytettiin m\u00e4\u00e4ritt\u00e4m\u00e4\u00e4n erot eri hiiriryhmien v\u00e4lill\u00e4. Tulokset. Lihavien hiiriryhmien H&E-v\u00e4rj\u00e4tyiss\u00e4 maksaleikkeiss\u00e4 rasvaa oli kertynyt selv\u00e4sti enemm\u00e4n hoikkiin hiiriin verrattuna. Lis\u00e4ksi liikunnan huomattiin v\u00e4hent\u00e4neen rasvan kertymist\u00e4 maksaan. Haiman saarekkeiden verisuonissa ei havaittu merkitsevi\u00e4 muutoksia. Haiman eksokriinisess\u00e4 kudoksessa verisuonten tiheys ja verisuonten suhde tumien lukum\u00e4\u00e4r\u00e4\u00e4n olivat yleisesti ottaen suurempia lihavien hiirten ryhmiss\u00e4 verrattuna hoikkiin hiiriin. Lihavilla, liikuntaa harrastamattomilla hiirill\u00e4 oli merkitsev\u00e4sti suurempi verisuonten tiheys kuin hoikilla hiirill\u00e4. Lis\u00e4ksi lihavilla liikuntaa harrastaneilla hiirill\u00e4 oli merkitsev\u00e4sti suurempi verisuonten tiheys kuin hoikilla liikkumattomilla hiirill\u00e4. Haiman saarekkeiden verisuonten tiheys, verisuonten suhteellinen osuus pinta-alasta ja Feret\u2019n halkaisija olivat merkitsev\u00e4sti suurempia kuin haiman eksokriinisen kudoksen. Johtop\u00e4\u00e4t\u00f6kset. Lihavilla hiirill\u00e4 oli havaittavissa taipumusta kapillaarien laajenemiseen haiman saarekkeissa. Pidempi interventiojakso voisi paljastaa merkitsev\u00e4mpi\u00e4 muutoksia. Lihavien hiirten eksokriinisess\u00e4 kudoksessa havaittu suurentunut verisuonten tiheys ja toisaalta pienempi Feret\u2019n halkaisija voivat viitata angiogeneesiin, jossa yksi verisuoni jakautuu kahdeksi. Liikunnan vaikutus verisuonistoon oli v\u00e4h\u00e4inen. 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Also, although physical activity has been shown to reduce the risk of these diseases, and despite the recognition of the importance of exercise, its positive effects at the cellular level are not yet fully understood. Therefore, this thesis aimed to investigate the changes that obesity and exercise induce on pancreatic capillary density and capillary area both together and separately using a mouse model. Methods. Adult C57BL/6J male mice (n=40) were randomized into four groups: 1) lean sedentary, 2) obese sedentary, 3) lean exercise, and 4) obese exercise. Obesity, hyperglycaemia and insulin resistance were induced using a Western diet for 18 weeks. Voluntary running for the exercise groups was started at ten weeks and lasted until the end of the study. Pancreas and liver sections were stained with haematoxylin-eosin (H&E) and with immunofluorescence. The image processing and analysis for pancreas sections were performed using Fiji/ImageJ software. 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spellingShingle Hasu, Outi Effects of Exercise and Obesity on Pancreatic Vasculature in Mice Pancreatic Vasculature Capillary Density Type 2 Diabetes Pancreatic islet Islet of Langerhans Liikuntafysiologia Exercise Physiology 5011 haima lihavuus hiiret liikunta diabetes sydän- ja verisuonitaudit verisuonet ylipaino insuliiniresistenssi aineenvaihduntahäiriöt pancreas obesity mice physical training cardiovascular diseases blood vessels overweight insulin resistance metabolic disorders
title Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
title_full Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
title_fullStr Effects of Exercise and Obesity on Pancreatic Vasculature in Mice Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
title_full_unstemmed Effects of Exercise and Obesity on Pancreatic Vasculature in Mice Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
title_short Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
title_sort effects of exercise and obesity on pancreatic vasculature in mice
title_txtP Effects of Exercise and Obesity on Pancreatic Vasculature in Mice
topic Pancreatic Vasculature Capillary Density Type 2 Diabetes Pancreatic islet Islet of Langerhans Liikuntafysiologia Exercise Physiology 5011 haima lihavuus hiiret liikunta diabetes sydän- ja verisuonitaudit verisuonet ylipaino insuliiniresistenssi aineenvaihduntahäiriöt pancreas obesity mice physical training cardiovascular diseases blood vessels overweight insulin resistance metabolic disorders
topic_facet 5011 Capillary Density Exercise Physiology Islet of Langerhans Liikuntafysiologia Pancreatic Vasculature Pancreatic islet Type 2 Diabetes aineenvaihduntahäiriöt blood vessels cardiovascular diseases diabetes haima hiiret insuliiniresistenssi insulin resistance lihavuus liikunta metabolic disorders mice obesity overweight pancreas physical training sydän- ja verisuonitaudit verisuonet ylipaino
url https://jyx.jyu.fi/handle/123456789/97364 http://www.urn.fi/URN:NBN:fi:jyu-202410106238
work_keys_str_mv AT hasuouti effectsofexerciseandobesityonpancreaticvasculatureinmice